ILA Flashcards
What are the 3 layers of the normal arterial vessel wall?
- tunica intima - simple squamous with connective basement membrane
- tunica media - middle layer of smooth muscle (often thickest)
- tunica adventitia - outermost made of elastin and collagen
What is a plaque composed of?
- necrotic and lipid core
- inflammatory cells (macrophages & T lymph)
- fibrous cap made from smooth muscle
- cellular lipids and debris
What leads to plaque formation?
Chronic or episodic exposure of arterial wall so plaques often form at branching sites
Formation of Plaques?
- damage to endothelial cells cause them to become more permeable. Lipids and inflammatory cells enter and form plaques.
> high levels of LDLs oxidise - macrophages phagocytose LDLs and release lipids as foam cells
> support migration of smooth muscle into
intima and increased collagen synthesis
> die and leak lipids –> fatty streak - foam cells release growth factors so smooth muscle proliferates into fibrous cap
- new vessels form (vasa vasorum) within plaque, expand, and haemorrhage causing plaque expansion
What are modifiable risk factors of atherosclerosis?
- smoking
- obesity
- hypertension
- sedentary lifestlye
- type 2 diabetes
- high cholesteral
What are some non-modifiable risk factors for atherosclerosis?
- age
- male gender
- family history
- race
- type 1 diabetes
Why does smoking cause atherosclerosis?
Damages endothelial cells due to free radicals, nicotine, and CO
Why does high cholesterol cause AS?
Increase in LDLs means more can oxidise and get stuck
Why does hypertension cause AS?
shearing force causes direct damage to endothelial cells
What race/ethnicity is AS more common in?
South Asian, African, Afro-Caribbean descent
Why is poorly damaged diabetes a risk factor for AS?
superoxide anions and glycosylation products cause high glucose levels in blood and more LDL oxidation. Also, loss of NO so less vasodilation and more platelet aggregation
What primary preventative measures for AS?
- exercise to redistribute LDLs
- more balanced diet to reduce weight
- reduce/stop smoking
What secondary preventatives for AS?
- statins for cholesterol
- antihypertensives
- diabetes control
- social prescribing
- dual antiplatelet therapy
Define anaphylaxis.
An acute allergic reaction to an antigen, to which the body has become hypersensitive. Severe, life-threatening, generalised, or systemic.
What is the criteria that needs to be met to classify a reaction as anaphylaxis?
- sudden onset and rapid progression of symptoms
- life threatening airway/breathing/circulation problems associated with skin and mucosal changes
- occurs within mins and can last a few hours
What are anaphylactoids?
trigger agent acts on mast cell rather than IgE and presents as idiopathic
What are some examples of trigger agents for anaphylaxis?
Food - peanuts, tree nuts, shellfish, eggs, lactose, gluten
Drugs - antibiotics, opioids, NSAIDs, anaesthetics
Venom - bee and wasp stings
Hospital - latex, plasters, radiocontrast injections
What type of hypersensitvity reaction is anaphylaxis?
Type 1 so involves IgE antibodies
What do IgE receptors bind to?
mast cells and basophils - antibodies primed so can react quickly when next come into contact with antigen
How is histamine released during anaphylaxis?
cross-linking causes rapid cellular degranulation and liberation of chemical mediators (histamine, protease, proteoglycans, dhemotactic)
What are the physiological responses of anaphylaxis?
- smooth muscle spasm in resp and GI tracts
- vasodilation/increased vascular permeability
- increased mucous secretion and bronchial smooth muscle tone
- decreased vascular tone, capillary leakage, hypotension, arrhythmia, syncope, shock
- histamine makes blood vessels/bronchioles leaky –> causes wheezing and shock due to large fluid loss from circulation
What is rapid assessment of anaphylaxis?
Airway, Breathing, Circulation, Disibility, Exposure
What guidelines for treatment of anaphylaxis?
- remove cause
- adrenaline into anterolateral middle thigh
What are the recommended dosages of adrenaline?
adults = 500ug, children < 12 = 300ug, children < 6 = 150ug
How does adrenaline relieve anaphylaxis?
- stimulates beta 1 receptors so HR and contraction increase
- stimulates beta 2 receptors so more bronchodilation
What can you do to alleviate anaphylaxis when more help is available?
- establish airway and high flow O2
- IV fluids
Why might a second dose of adrenaline be needed?
short half life of 2-3 mins
What is the confirmatory blood test for anaphylaxis?
mast cell tryptase - elevated up to 6 hours after
What are risk factors for anaphylaxis?
- those with other allergies
- older age, women > men
- new allergens and pollutants
- increase in antibiotics
- more caesarean births
- more processed diets
These all mean less exposire to healthy gut microbiome and weaker immune system.
What two characteristics should drugs have to be able to act quickly, specifically analgesics?
- Low protein binding - protein binding lowers free concentration so if low then high plasma concentration
- High lipid solubility - allows drug to cross BBB through astrocytes
What is the difference between volatile and IV anaesthetic?
Gas can be kept at a good level whereas IV isn’t as sustainable - it builds up and happens more quickly.
What is an agonist?
A compound that binds to a receptor and activates it to produce a response
What is an example of an agonist?
Adrenaline is agonist of B-adrenoreceptors because it increases heart rate
What is a full agonist?
High efficacy so produces full repsonse whilst occupying low proportion of receptors
What is a partial agonist?
Sub-maximal activation even when all receptors occupied
What is an inverse agonist?
Produces opposite effect to agonist but binds to same site on receptor
What is an antagonist?
Compound that prevents agonist from binding to a receptor and reduces effect of agonist
Example of antagonist?
Propranolol prevents tachycardia
What is a competitive antagonist and give example.
- reversible and surmountable
- binds to same site
- increasing agonist undoes action
Eg. naloxone for opioid receptor
What is a non-competitive antagonist and give example.
- irreversible and insurmountable
- binds to allosteric site
Eg. ketamine and NMDA-glutamate receptor.
Example of enzyme drug target?
ACE Inhibitors
Example of transporter drug target?
PPIs
Example of ion channel drug targets?
Amlodipine CCB
Definition of bioavailability.
How much a drug is available over a given time in systemic circulation.
IV is 100%, oral is always lower
What is first pass metabolism?
Metabolism of a drug into inactive compounds in the liver, after enteric absorption but before it reaches the systemic circulation
Pathway of drug to liver?
intestinal lumen –> intestinal wall –> membrane transporters –> liver
Is dose of morphine higher when given orally or IV?
Orally
Why are lower doses/longer intervals of morphine used for patients with renal impairement?
Morphine matabolised to morphine 6 glucuronide which is more potent and renally excreted.
If renally impaired, this could build up and cause respiratory depression due to high opioid sensitivity and reduced renal clearance.
Why does opioid excess affect lungs?
Opioids activate receptors on neurones with respiratory centres.
Difference in presentation between arterial and venous thrombosis: pulse?
A: dimished or absent pulse
V: pulse is present
Difference in presentation between arterial and venous thrombosis: pain?
A: pain is intermittent claudication
V: pain is aching and cramping with oedema
Difference in presentation between arterial and venous thrombosis: skin pigmentation?
A: skin dependent rubor
V: pigmentation in gaiter area (medial and lateral malleolus)
Difference in presentation between arterial and venous thrombosis: nails?
A: thickened and ridged
V: N/A
What are the 6Ps of arterial thrombosis?
Pulselessness, pain, pallor, paralysis, perishingly cold, paraesthesia
Difference in presentation between arterial and venous thrombosis: clot colour?
A: white
V: red
What blood test is done to confirm diagnosis of DVT?
D-Dimer test - detects pieces of blood clot that have been broken down
Why is the D-dimer test sensitive but not specific?
Sensitive because high percentage of positive results, easily picks up raised D-dimers. Not specific because other things can increase it such as DIC, infection, pregnancy, malignancy.
What drugs are used in the treatment of a DVT?
Heparin and warfarin
How does warfarin work?
Exhibits anticoag effects via extrinsic and intrinsic pathways. limits synthesis of vit K dependent clotting factors (10,9,7,2) by inhibitng vit k reductase complex
How does heparin work?
catalyst for antithrombin III which inactivates proteases in coagulation cascade by producing confirmational change
What is the biggest complication of a DVT?
PE
What are some risk factors for Virchow’s triad?
- increase in age –> increases viscocity
- long haul flights –> increases stasis so flow is not laminar
- hypertension –> shearing forces on endothelial cells
- smoking –> damages vessel walls due to free radicals, nicotine, and CO
- overweight –> increases chances of plaque formation
What is the diagnostic criteria for an AKI?
- rise in creatinine > 25 umol/l in 48 hrs
- rise in creatinine > 50% in 7 days
- urine output < 0.5 ml/kg/hr for > 6 hours
What are the three major classes of AKI?
- pre-renal
- intrinsic/renal
- post renal
What are examples for each of the classifications of an AKI?
- dehydration, hypotension, heart failure
- glomerulonephritis, interstitial nephritis, acute tubular necrosis
- kidney stones, abdo/prostate cancers, ureter/urethral strictures
What is the main complication of AKI?
hyperkalaemia
What changes does hyperkalaemia show on ECG?
- Tall T waves
- flattened p waves
- prolonged PR interval
- ST depression
What drugs are contraindicated in an AKI? (DAMN)
Diuretics
ACE Inhibitors
Metformin
NSAIDs
Definition of a stroke?
Acute neurological deficit lasting more than 24hrs and caused by cerebrovascular aetiology
What are the two main types of stroke?
Ischaemic and Haemorrhagic
What is the definition of a transient ischaemic attack (TIA)?
Transient episode of neurolgical dysfunction caused by ischaemia, without acute infarction. Effects will completely resolve within 24hrs
What is the definition of amaurosis fugax?
Painless and transient visual disturbance/loss of vision due to atherosclerosis/thromboembolism in internal carotid or ophthalmic arteries.
How does AF increase the risk of stroke?
Fibrillation causes stasis and pooling of blood, increasing likelihood of clot formation in the heart - and therefore embolism to the brain
Are stroke symptoms ipsilateral or contralateral to area of brain affected?
Contralateral to area of ischaemia because motor and sensory nerve fibres decussate in either the spinal cord or brainstem.
What is Cushing’s reflex?
Response to acute increase in ICP - resulting in hypertension, bradycardia, and erratic breathing
What is the pathophysiological process of Cushing’s refflex?
- Ischaemia increases until ICP exceeds that of arterial BP in brain, causing it to compress
- Alpha 1 adrenergic receptors cause arterial smooth muscle will vasoconstrict (sympathetic) in order to increase the blood pressure and reperfuse the brain –> hypertension
- This causes baroreceptors in the aortic arch to simultaneously reduce the blood pressure (parasympathetic) –> bradycardia and stomach ulcers
- The HTN then presses on resp. centres in brain stem –> irregular breathing
Why is Cushing’s reflex a bad sign?
Suggests brain herniation and death is imminent
